title: Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1 diabetes in Tunisians.
abstract: Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing β-cells. Several studies support the involvement of T cell activation molecules. In order to underline the role of the genes involved in this pathway, we investigated, using the Sequenom MassARRAY platform, polymorphisms of sixteen single-nucleotide polymorphisms (SNPs) belonging to PTPN22, CD28, CTLA-4, and ZAP-70 genes in 76 T1D patients and 162 unrelated healthy controls from Southern Tunisia. We confirmed the association with PTPN22 (rs2476601, Corrected P (Pcorr)=0.002, OR=6.20) and CD28 gene (rs1879877, Pcorr=0.003; OR=4.27 and rs3181096, Pcorr=0.02; OR=1.73). We also identified an association with rs17695937 of ZAP-70 gene (Pcorr=0.02, OR=1.87). Our results suggest a significant effect on T1D susceptibility for A-C-A-G-C and T-C-C-T-A-C haplotypes, of ZAP-70 and CD28 genes, respectively. In addition, (A-G-C) combination of ZAP-70/CD28 gene was significantly increased in T1D patients as compared to controls, suggesting the possible interaction between these genes. These results confirm the involvement of PTPN22 and CD28 genes in the genetic susceptibility to T1D. Interestingly, ZAP-70 seems to contribute to the susceptibility to the disease in our population. However, this finding has to be confirmed in further studies.
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, Tunisia; University of Sfax, Tunisia. Electronic address: zouidi_ferjeni@yahoo.fr.
authors.forename: Ferjeni
authors.initials: F
authors.lastname: Zouidi
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.forename: Dorra
authors.initials: D
authors.lastname: Bouzid
authors.forename: Hajer
authors.initials: H
authors.lastname: Fourati
authors.forename: Olfa
authors.initials: O
authors.lastname: Abida
authors.forename: M Ben
authors.initials: MB
authors.lastname: Ayed
authors.forename: Thouraya
authors.initials: T
authors.lastname: Kammoun
authors.forename: Monjia
authors.initials: M
authors.lastname: Hachicha
authors.forename: Carlos
authors.initials: C
authors.lastname: Penha-Gonçalves
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
mesh_terms: D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D051746:ZAP-70 Protein-Tyrosine Kinase; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: CD28; CTLA-4 genes; HWE; Hardy–Weinberg equilibrium; LD; OR; PTPN22; T1D; Tunisia; Type 1 diabetes; ZAP-70; linkage disequilibrium, haplotype; odds ratios; type 1 diabetes